Xenopus laevis has long been used successfully as the ectothermic vertebrate species of choice for studying the phylogeny of the complex immune system. In addition, X. laevis has proved to be an excellent model system for answering fundamental immunological questions that are not phylogenetically restricted to a given taxon. In part, this is because development of the Xenopus immune system occurs at two distinct times: once during larval life, and then again during the metamorphic transition from immunocompetent larva to immunocompetent adult. Since the larval form is free-swimming and amenable to a variety of surgical and nonsurgical interventions, valuable information can be obtained that is not possible to obtain from in utero studies of mammals (e.g., development of self-tolerance to adult specific antigens, acquisition of a second T-cell repertoire, and ontogeny of T-cell subsets in a natural setting). Moreover, metamorphosis is hormonally driven which permits examination of immunologically relevant neuroendocrine-immune system interactions in a developing immune system. Another critical aspect of Xenopus immunology that makes it important as a model is the well-documented absence of classical and non-classical MHC class I expression during the pre-metamophic larval period. Finally, transplantable tumor cell lines that either express or lack MHC class I and II molecules also contribute to the use of Xenopus as a naturally-occurring "knockout" species. The broad objectives of this proposal are to further develop Xenopus laevis as a non-mammalian immunobiologically-focused model by: (1) assuring the systematic breeding and husbandry of different clones, strains, and species of Xenopus;(2) organizing a central repository of information and existing research materials (e.g., cell lines, DNA libraries, mAbs, animals) readily available to the scientific community;and (3) generating new tools for immunological research (e.g., new mAbs, cDNA libraries, cells lines, transgenics frogs). Many areas of existing and new research should benefit from satisfying these aims. We envision: further development of X. laevis as: a nonmammalian model for studying: (1) tumor immunity;(2) self-tolerance and autoimmunity during ontogeny;(3) host-pathogen interactions;(4) genome evolution and genomic regulation;(5) immunotoxicology (e.g. endocrine disruptors);(6) the role of heat shock proteins in immunity;(7) the function of nonclassical MHC class I antigens;and (8) the evolution of toll-like receptors (structure and function) in immunity.